Effects of a Fucoidan on the Activation of Plasminogen by u-PA and t-PA

The effect of an anticoagulant fucoidan (C-I-H) from the brown seaweed Ecklonia kurome on the fibrinolytic system was studied in vitro using S-2251 as a substrate of plasmin. C-I-H enhanced the activation of Glu- and Lys-plasminogen by high molecular weight urokinase-type plasminogen activator (HMW u-PA) very effectively, but the activation by low molecular weight u-PA was hardly enhanced with C-I-H. C-I-H also potentiated moderately the activation by single- and two-chain tissue-type plasminogen activators (sct- and tct-PA). These effects of C-I-H were higher than those of heparin used. But C-I-H had no effect on the amidolytic activity of plasmin to S-2251. These results indicate that C-I-H promotes the generation of plasmin in the plasminogen activation by HMW u-PA and t-PA, but not the activity of generated plasmin. Kinetic analyses suggest that C-I-H enhances the HMW u-PA-mediated plasminogen activation by increasing the affinity of the activator for Glu- and Lys-plasminogen and by increasing the molecular activity of the activator. On the other hand, C-I-H had no effect on the affinity of tct-PA for both plasminogens. The catalytic efficiencies of HMW u-PA and tct-PA for the activation of both plasminogens were increased with C-I-H about 8- and 2-fold, respectively. The present results suggest that C-I-H has the fibrinolytic activity by stimulating the plasminogen activation by HMW u-PA and t-PA. The mechanism of the enhancement effect of C-I-H on the activation is presumed to be that C-I-H binds to plasminogen, thereby inducing a structural change of plasminogen susceptible to the action of plasminogen activators.